White Matter Lesions as a Predictor of Depression in the Elderly: The 3C-Dijon Study

Neuroepidemiology, Institut National de Santé et de Recherche Médicale, Paris, France.
Biological psychiatry (Impact Factor: 10.26). 05/2008; 63(7):663-9. DOI: 10.1016/j.biopsych.2007.09.006
Source: PubMed


There is increasing evidence for a link between cerebrovascular disease and depression in the elderly but the mechanisms are still unknown. This study examines the longitudinal relationship between depression and white matter lesions (WML) in a sample of elderly aged 65 years and older.
Three City (3C)-Dijon is a 4-year follow-up population-based prospective study of 1658 subjects. At baseline, lifetime major depressive episode diagnosis was established using the Mini International Neuropsychiatric Interview. At each study wave, severity of depressive symptoms was assessed using Center for Epidemiological Studies-Depression (CES-D), and antidepressants intake was recorded. At baseline, lifetime major depression (LMD) was defined as lifetime major depressive episode or antidepressant medication intake. At follow-up, subjects were classified "incident depression" if scoring high at CES-D or antidepressant users. At baseline, cerebral magnetic resonance imaging (MRI) was performed to quantify WML volumes using an automated method of detection. At 4-year follow-up, 1214 subjects had a second MRI.
Cross-sectional analysis showed a significantly higher WML volume in subjects with LMD compared with other subjects. Adjusted longitudinal analysis showed that increase in WML load was significantly higher in subjects with baseline LMD (2.1 cm(3) vs. 1.5 cm(3), p = .004). Among subjects free of depression up to baseline (n = 956), the higher the baseline WML volume, the higher the risk of developing depression during follow-up (odds ratio one quartile increase: 1.3; 95% confidence interval: = 1.1-1.7).
Our data show that depression and WML volumes are strongly related. These results are consistent with the hypothesis of a vascular depression in the elderly.

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Available from: Bernard Mazoyer, Oct 05, 2015
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    • "Basically the premutation may be more vulnerable to environmental toxicity including chronic methadone use. Some other factors might also contribute to progression of WMD, such as depression [Fields 2008; Godin et al., 2008], hypertension [Godin et al., 2011; Hamlin et al., 2012], and chronic pain [Buckalew et al., 2013] "
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    ABSTRACT: The fragile X-associated tremor ataxia syndrome (FXTAS) is caused by the premutation in FMR1 gene. Recent reports of environmental toxins appear to worsen the progression of FXTAS. Here we present a case of male adult with FXTAS and a long history of methadone use. The patient shows a faster progression in both symptoms of disease and MRI changes compared to what is typically seen in FXTAS. There has been no research regarding the role of narcotics in onset, progression, and severity of FXTAS symptoms. However, research has shown that narcotics can have a negative impact on several neurodegenerative diseases, and we hypothesize that in this particular case, methadone may have contributed to a faster progression of FXTAS as well as exacerbating white matter disease through RNA toxicity seen in premutation carriers. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 04/2015; DOI:10.1002/ajmg.a.37030 · 2.16 Impact Factor
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    • "Late-life major depression has been consistently linked to brain abnormalities. Many neuroimaging studies have found that late-life major depression is associated with decreased medial frontal gray matter volume [10], [11] and an increased number of white matter lesions (WMLs) [12], [13], but the relationship between late-life major depression and limbic system abnormalities remains unclear [14]–[16]. Late-life subsyndromal depression could be related to these brain structures if it shares common neuroanatomical substrates with late-life major depression. "
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    • "Three-dimensional (3D) high-resolution T1-weighted brain volume was acquired using a 3D inversion recovery fast spoiled-gradient echo sequence and T2-and proton density (PD)eweighted brain volumes were acquired using a 2-dimensional dual spin echo sequence with 2 echo times. Images were sent to the database repository (Godin, et al., 2008), where they were analyzed with the optimized Voxel-Based Morphometry protocol (Good, et al., 2001), using Statistical Parametric Mapping 99, modified to take into account structural characteristics of the aging brain (Godin, et al., 2009; Lemaitre, et al., 2005). Gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes were estimated as the integral of voxel intensities over the respective modulated tissue partition images; total intracranial volume was computed as their sum, and total brain volume (TBV) as the sum of GM volume (GMV) and WM volume. "
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